Features of Conclusion of Electronic Transactions Requiring a Notarial Certificate

The urgency and urgent necessity to develop a research topic are due to a number of factors. First of all, the legal community unanimously reached a consensus on the necessity to reform the institution of notaries in the direction of expanding the powers and functions of public and private notaries, increasing the requirements for these participants in the context of the procedure of certification of transactions (contracts) in various fields. The reform of the Ukrainian notary has recently exhausted its potential and positive expectations on the part of civil society, which is only complicated by the progressive situation with the spread of acute respiratory infections caused by the COVID-19 SARS-CoV-2 virus. The purpose of this article was to objectively outline the existing problems in the field of law enforcement, related to the peculiarities of electronic transactions that require notarization, with the formulation of author's proposals to improve legislation in this area. The study was conducted using a number of general and special methods, a key role among which was played by comparative legal and statistical-prognostic methods, which were used to thoroughly analyze the current state of affairs in the field of electronic certification of transactions by notaries. As a result of the study, the authors concluded that in the development of the global information society and digital economy, the issue of electronic transactions requiring notarization needs further involvement of both theoretical and scientific research, as well as the development of practical solutions and proposals to improve the electronic interaction system. Keywords: Transaction, a notary, the notary, notarized transaction, digitalization

Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways

Translocation of Inhaled Ultrafine Manganese Oxide Particles to the Central Nervous System

BACKGROUND: Studies in monkeys with intranasally instilled gold ultrafine particles (UFPs; < 100 nm) and in rats with inhaled carbon UFPs suggested that solid UFPs deposited in the nose travel along the olfactory nerve to the olfactory bulb. METHODS: To determine if olfactory translocation occurs for other solid metal UFPs and assess potential health effects, we exposed groups of rats to manganese (Mn) oxide UFPs (30 nm; ~ 500 μg/m(3)) with either both nostrils patent or the right nostril occluded. We analyzed Mn in lung, liver, olfactory bulb, and other brain regions, and we performed gene and protein analyses. RESULTS: After 12 days of exposure with both nostrils patent, Mn concentrations in the olfactory bulb increased 3.5-fold, whereas lung Mn concentrations doubled; there were also increases in striatum, frontal cortex, and cerebellum. Lung lavage analysis showed no indications of lung inflammation, whereas increases in olfactory bulb tumor necrosis factor-α mRNA (~ 8-fold) and protein (~ 30-fold) were found after 11 days of exposure and, to a lesser degree, in other brain regions with increased Mn levels. Macrophage inflammatory protein-2, glial fibrillary acidic protein, and neuronal cell adhesion molecule mRNA were also increased in olfactory bulb. With the right nostril occluded for a 2-day exposure, Mn accumulated only in the left olfactory bulb. Solubilization of the Mn oxide UFPs was < 1.5% per day. CONCLUSIONS: We conclude that the olfactory neuronal pathway is efficient for translocating inhaled Mn oxide as solid UFPs to the central nervous system and that this can result in inflammatory changes. We suggest that despite differences between human and rodent olfactory systems, this pathway is relevant in humans

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.Fundacao de Amparo Pesquisa do Estado de Sao Paulo-FAPESP[07/07139-3]Coordenaco de Aperfeioamento de Pessoal de Nivel Superior-CAPESInstituto Nacional de Ciencia e Tecnologia de Complexos Fluidos (INCT)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNP

GABA and GABAergic Interneurons During Corticogenesis: MigrationFunctional Maturation, and Consequences of Gestational Ethanol Exposure,

Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Interdepartmental Graduate Program in Neuroscience, 2008.Migration during corticogenesis plays an important role in orchestrating the assembly of cortical neurons within the laminated layout of the neocortex. Pyramidal cells migrate radially from the ventricular zone of the cortex while the majority of GABAergic neurons migrate tangentially from the medial ganglionic eminence (MGE). One of the factors that has been postulated to regulate the migration of cortical cells is the neurotransmitter GABA due to the early expression of GABA and its receptor, before the formation of synapses. The results of experiments present in this thesis uncover a role for GABA in regulating the migration of primordial GABAergic cells, mainly those arising from the MGE, as well as a developmentally dynamic expression of GABAA receptor subunits in this population of cells. Transgenic mice lines in which the expression of GFP is driven by either the expression of the GABA-producing enzyme, glutamic acid decarboxylase (GAD), or the gene Lhx6, whose CNS expression is limited to cells derived from the MGE, were used to examine the in vivo disposition of putative GABAergic cells or MGE-derived cells, respectively. A combination of experimental approaches including slice cultures, whole-cell patch clamp recording, immunohistochemistry and single-cell RT-PCR, were used to demonstrate the presence of ambient GABA along the tangential migratory path of MGE-derived cells. We demonstrate further that ambient GABA, through activation of GABAA receptors modulates the cortical entry of tangentially migrating MGE-derived cells. Increases or decreases in ambient levels of GABA or GABAA receptor function can increase or decrease the number of MGE-derived cells that enter into the neocortex, respectively. MGE-derived cells acquire increased sensitivity to GABA as they migrate, and this observation led to revealing the dynamic expression of GABAA receptor number and isoforms in tangentially migrating MGE-derived cells. Errors in the migration process and subsequent development of cortical cells, specifically GABAergic cortical interneurons, have been implicated in disorders with developmentally etiology such as schizophrenia, epilepsy, and autism, as well in consequences of prenatal exposure to teratogens, notably ethanol. Previous studies have suggested that prenatal exposure to ethanol compromises GABAergic transmission. In this light, this thesis tested the hypothesis that prenatal exprosure to ethanol affects the tangential migration and development of primordial cortical GABAergic interneurons through ethanol’s interaction with the developing GABAergic system. Our results demonstrate an increase in tangential migration, resulting in a net increase in the number of MGEderived cells with in utero ethanol exposure. This ethanol-induced increase in migration occurs concurrently with an increase in ambient GABA along the migratory path and alterations in the subunit composition of GABAA receptors expressed by MGE-derived cells. Our data implicate GABA as an important regulation of corticogenesis and establish the basic framework for investigating how cortical development might be affected by maternal ethanol consumption

Methamphetamine-induced Neuroinflammation and Neurotoxicity:a Role for Interleukin-1β

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Neurobiology and Anatomy, 2012.Methamphetamine (MA) is a potent, addictive psychostimulant abused by millions of people worldwide. MA exposure induces neurotoxicity, particularly in the striatum, where it damages dopaminergic terminals. In parallel with this neurotoxicity, MA also induces neuroinflammation, characterized by activation of striatal microglia and astrocytes, leading to production of pro-inflammatory cytokines and reactive oxygen species. It is unclear whether MA-induced neuroinflammation contributes to MAinduced neurotoxicity. To address this issue, we examined the time course and dose response of MA-induced neurotoxicity and neuroinflammation to search for time- and dose-specific links between the two, using a binge dosing paradigm of four injections given every two hours to mimic human use patterns; we also focused on the specific contributions of the pro-inflammatory cytokine interleukin-1β (IL-1β) and the inflammation-associated oxidative enzyme NADPH oxidase 2 (NOX2). We found that treatment with at least 4 mg/kg MA per injection decreased striatal dopamine, tyrosine hydroxylase, and dopamine transporter levels within one day, and that these decreases persisted for at least one week. Striatal microglia and astrocytes were both activated one day after binge MA treatment of all doses, including those that did not induce measurable neurotoxicity; while astrocyte activation persisted, microglial activation attenuated during the two weeks of the study. Despite this gliosis, we did not find altered mRNA expression of the pro-inflammatory cytokines tumor necrosis factor α, interleukin 6, or chemokine (C-C motif) ligand 2 in the striatum. IL-1β knock-out (KO) mice were resistant to MA-induced neurotoxicity, and local overexpression of IL-1β exacerbated MA-induced neurotoxicity. However, we were unable to find an increase in striatal IL- 1β expression in the hours and days following MA exposure, suggesting that MAinduced IL-1β upregulation and signaling may primarily occur elsewhere, or may be too subtle or rapid for us to detect. Finally, although MA exposure increased NOX2 mRNA expression in the striatum, NOX2 KO mice were not protected against MA-induced neurotoxicity or glial activation. These findings give insight into the complex relationship between MA-induced neuroinflammation and neurotoxicity